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November 3, 2005

Anti-aging Hormone Reduces Reactive Oxygen Species

Topics: Medicine

Back in January of 2002, a group of scientists reported in the Jan. 15 online version of the Proceedings of the National Academy of Sciences, that "Klotho," a gene named for the Greek Fate purported to spin the thread of life, contributes to life expectancy in humans. Studying more than 2,000 anonymous samples from three ethnically distinct groups of people, the scientists found that having two copies of a less-common version of klotho is twice as prevalent in infants as in people over age 65. These results suggested that people born with the two copies die sooner than others, although the gene's exact influence on health and aging were not then known.

But now, a new study shows that this protein acts by increasing the cell's ability to detoxify harmful reactive oxygen species, in other words, it reduces oxidative stress. Oxidative stress is the harmful condition that occurs when there is an excess of free radicals (also here) , a decrease in antioxidant levels, or both.

The research appears as the "Paper of the Week" in the November 11 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

The klotho gene product, or Klotho protein, is secreted in the blood and functions as an anti-aging hormone. A defect in the klotho gene in mice leads to a syndrome closely resembling human aging, while overexpression of the gene extends lifespan in mice.

Now Makoto Kuro-o, assistant professor of pathology at the University of Texas Southwestern Medical Center at Dallas, has discovered one way in which Klotho extends lifespan. Using both cultured cells and transgenic mice, the researchers showed that Klotho increases resistance to oxidative stress.

"Increased longevity is always associated with increased resistance to oxidative stress," explains Kuro-o. "Oxidative stress causes the accumulation of oxidative damage to important biological macromolecules such as DNA, lipids, and proteins that would result in functional deterioration of the cell, which eventually causes aging."

"In this study," says Kuro-o, "we propose that Klotho does its job by increasing the ability of the cell to detoxify harmful reactive oxygen species, thereby increasing resistance to oxidative stress of the body." The protein acts by turning on an enzyme called manganese superoxide dismutase. This enzyme, found in the mitochondria of the cell, then hydrolyzes harmful superoxide into less harmful hydrogen peroxide.

This research may eventually lead to the development of anti-aging drugs, a long-standing goal of many pharmaceutical companies. "We showed that the anti-aging hormone Klotho confers resistance to oxidative stress in cells and animals," says Kuro-o. "This means that Klotho protein itself or small molecule mimetics may be potentially useful as anti-aging medicines."

Also of interest, especially in light of "Klotho." is the fact that gene expression can be influenced by, among other factors - nutrition. For example - Control of Gene Expression by Fatty Acids, and Amino acids as regulators of gene expression, and in general, Genetics and nutrition.

Posted by Hyscience at November 3, 2005 11:47 PM



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